Synapsins: Structure and Function in Neurotransmission

描述(由申请人提供)：神经系统执行复杂任务的能力，如感官感知、学习和协调运动，依赖于化学突触处神经递质的动态释放。神经递质的分泌涉及到一个严格调控的过程，即将突触小泡运输到神经末梢的质膜上，在那里它们融合并释放神经递质到突触后受体。调节突触动力学的一个关键成分是神经元控制可融合突触小泡数量的能力。突触蛋白家族被认为在这一调节中发挥作用。这项提议的目的是进一步阐明突触蛋白的功能(S)。目的探讨突触素I和突触素II的不同功能，以及它们的功能是否通过影响三磷酸腺苷结合的突变来依赖三磷酸腺苷。目的II将确定蛋白激酶A对突触蛋白的磷酸化是否是使突触小泡进入“容易释放”状态所必需的。AIM III将确定保守的突触素E结构域的功能以及与该结构域结合的蛋白质。了解蛋白质在神经传递中的功能可能有助于阐明疾病相关突触功能障碍的原因。

DESCRIPTION (provided by applicant): The ability of the nervous system to perform complex tasks such as sensory perception, learning, and coordinated movement relies on the dynamic release of neurotransmitters at chemical synapses. The secretion of neurotransmitters involves a tightly regulated process of trafficking synaptic vesicles to the plasma membrane of nerve terminals where they fuse and release neurotransmitters onto postsynaptic receptors. A key component in the regulation of synaptic dynamics is the ability of the neuron to control the number of fusable synaptic vesicles. A family of proteins, synapsins, is proposed to play a role in this regulation. This proposal's goal is to further elucidate the function(s) of synapsins. Aim I will address the differential function of synapsin I and II and whether their function is ATP-dependent through mutations affecting ATP binding. Aim II will determine whether phosphorylation of synapsins by protein kinase A is necessary for the movement of synaptic vesicles into a 'readily releasable' state. Aim III will identify a function for the conserved synapsin E domain and proteins that bind to this domain. Knowledge of protein function in neurotransmission may help elucidate the cause of disease related synaptic dysfunction.